Membrane bioreactors, which use biological matter in conjunction with a membrane to convert materials supplied to the biological matter, may be used for bioreaction applications such as the production of useful substances, for example pharmaceuticals, antibodies or vaccine components, the bioconversion of organic wastes into biomass or biofuels, or remediation of toxic wastes including degradation of toxic chemicals to inert or non-bioavailable forms and precipitation or reduction/oxidation of heavy metals.
Broadly speaking, existing bioreactors can be classified as mechanically agitated bioreactors, pneumatically agitated bioreactors or non-agitated bioreactors. Mechanically agitated bioreactors include: aeration-agitation bioreactors; rotating drum bioreactors; and spin-filter bioreactors. Pneumatically agitated bioreactors include sparge bioreactors, and air-lift bioreactors. Non-agitated bioreactors include gaseous phase bioreactors, oxygen-permeable membrane aerator bioreactors, and overlay aeration bioreactors.
Pneumatically agitated bioreactors typically consist of a vat fitted with aeration vents that sparge air through the contained liquid medium, to maintain an adequate supply of dissolved oxygen for the biomass. Such reactors use a variety of systems to ensure that the biomass and process liquor remain well mixed, including impellers, propellers, and paddles. Paddles are also used to scrape biomass from the sides of the vessel to minimise fouling and ensure that the biomass remains in contact with the process liquor. However a disadvantage with such systems is that the shear forces associated with such mixing and scraping can often damage fragile cultures, leading to a reduction in biological activity and a consequent reduction in productivity. As well, the presence of the biomass, which is relatively dense, increases the viscosity of the reaction medium, thus reducing both mixing efficiency and the rate of diffusion of molecular oxygen and other gases within the process stream. Any reduction in the availability of oxygen leads to a corresponding reduction in the activity of the biomass, ensuring that many cell types no longer function as they would in natural systems (e.g. at the air-solid interface or, in the case of animal cells, while bathed in blood).
Tissue culture systems include sparged bioreactors and a variety of submerged surface-growth systems in culture vessels or rolling drums. A disadvantage of these systems is that the uptake of oxygen is relatively low, and hence the bioavailability of dissolved oxygen becomes limiting once small amounts of biomass have grown. The low availability of dissolved oxygen prevents many types of cells from being cultured, and many cell lines do not function as they would in the body, where oxygen is more readily available.
In packed column systems, cells are immobilised on inert materials of various shapes such as rings, spheres saddles or polygons which are packed into a column. A nutrient stream is oxygenated prior to being fed to the column. A disadvantage of these systems is that they are limited by the solubility of oxygen in the nutrient stream. They are usually run in trickling mode and oxygen limitation may also relate to thickness of the biomass. A further disadvantage is that growth of the cells can lead to agglomeration of the packing and to clogging of the column. Cost is also an issue for highly engineered versions of these.
Membrane systems may be classified into one of three broad classes:
Type 1: Gas-Liquid Interface Membrane Bioreactors involve the use of a porous membrane host, which is used to support the active biomass on the gas side of the membrane. The other side of the membrane is in contact with the process liquor, which is pumped through the membrane under pressure. A sintered ceramic membrane has been reported for this process (Canto et al, Science and Engineering Journal, 1998-2, 2). The sintered ceramic membrane reported was relatively impermeable, so the liquid was pressurized to pump it through the membrane. A disadvantage with this type of bioreactor is that the elevated pressures at which such reactors operate restrict the size of the membrane and its housing, to avoid breakage. The reduced availability of nutrients (due to the relatively low total porosity of the active membrane) restricts the growth of the biomass, thus leading to relatively low product yields. A further example of this type is described in WO90/02170. This patent describes a hollow fibre membrane having a biolayer (biofilm) on the outside. In use, liquid is passed through the lumen of the membrane, and air is provided to the biofilm through a support matrix surrounding the membrane. A disadvantage with this system is that, due to the significant transmembrane pressures required, the support matrix is required around the membrane to prevent damage due to that pressure. The construction of a concentric support matrix/biofilm/membrane system is complex. In addition, it is likely that the support matrix would become fouled with cells from the biofilm in use, leading to reduced diffusion rates of oxygen and nutrients through the biofilm.
Type 2: The culture is grown on the liquid side of the membrane, often under anoxic conditions. In an example, a porous hollow-fibre membrane has been used to immobilize a biofilm in contact with the liquid medium, while oxygen-containing gas is supplied to the other side of the membrane (JP2003251381 Asahi Kasei Corp.). A second patented method has pressurized hydrogen gas introduced into hollow fibers that are sealed at one end to prevent the escape of the hydrogen, and are impervious to liquids. Water surrounds the fibres and a biofilm grows on the liquid side of the membrane using dissolved hydrogen as an electron donor for the cells to remove oxidized chemicals dissolved in the liquid (U.S. Pat. No. 6,387,262, Northwestern University). A disadvantage of such systems is that the gas is provided to the membrane under pressure, necessitating expensive equipment for pressurizing and for housing the pressurised gas. In addition, the specialised membranes required are expensive and require sophisticated equipment for their manufacture.
Type 3: The culture is grown suspended in liquor and filtered from the liquor using a membrane filter. Most membrane bioreactors are type 3. The disadvantages of this class of bioreactor are similar to those of air-lift and tissue culture type bioreactors, and they also suffer from the disadvantages of biofouling of the membrane used to separate the liquor that contains product materials.
There is therefore a need for a bioreactor which is inexpensive, durable, and which can provide for higher rates of bioconversion than conventional systems.